Organometallic 2-cyano-2-aminobenzoate-propyl derivates and their use as anthelmintics

Abstract

The invention relates to compounds characterized by a general formula (1), wherein X is a group described by a general formula —K p —F l —K q —, wherein F l is —C(═O)—, —C(═S)—, with l being 0 or 1, K p is a C p -alkyl with p being 0, 1, 2, 3 or 4, K q is a C q -alkyl with q being 0, 1, 2, 3 or 4, and wherein n of R 1 n is 0, 1, 2, 3, 4 or 5, and each R 1 independently from any other R 1 is —C(═O)OR 2 , —C(═O)NR 2 2 , —C(═O)SR 2 , —C(═S)OR 2 , —C(NH)NR 2 2 , CN 4 H 2 , —NR 2 2 , —C(═O)R 2 , —C(═S)R 2 , —OR 2 , —SR 2 , —CF 3 , —OCF 3 , —SCF 3 , —SOCF 3 , —SO 2 CF 3 , —CN, —NO 2 , —F, —Cl, —Br or —I, with each R 2 independently from any other R 2 being a hydrogen or C 1 -C 4 alkyl, and wherein OM is an organometallic compound independently selected from the group of an unsubstituted or substituted metal sandwich compound, an unsubstituted or substituted half metal sandwich compound or a metal carbonyl compound and their use in a method for treatment of infections by helminths.

The invention claimed is: 
     
       1. A compound characterized by a general formula (1), 
       
         
           
           
               
               
           
         
         wherein X is a group described by a general formula —K p —F l —K q —, wherein
 F l  is —C(═O)—, —C(═S)—, with l being 0 or 1, 
 K p  is a C p -alkyl with p being 0, 1, 2, 3 or 4, 
 K q  is a C q -alkyl with q being 0, 1, 2, 3 or 4, and wherein 
 
         n of R 1   n  is 0, 1, 2, 3, 4 or 5, and 
         each R 1  independently from any other R 1  is —C(═O)OR 2 , —C(═O)NR 2   2 , —C(═O)SR 2 , —C(═S)OR 2 , —C(NH)NR 2   2 , CN 4 H 2 , —NR 2   2 , —C(═O)R 2 , —C(═S)R 2 , —OR 2 , —SR 2 , —CF 3 , —OCF 3 , —SCF 3 , —SOCF 3 , —SO 2 CF 3 , —CN, —NO 2 , —F, —Cl, —Br or —I, 
         with each R 2  independently from any other R 2  being a hydrogen or C 1 -C 4  alkyl, and wherein OM is an organometallic compound independently selected from the group of an unsubstituted or substituted metal sandwich compound, an unsubstituted or substituted half metal sandwich compound or a metal carbonyl compound. 
       
     
     
       2. The compound according to  claim 1 , wherein n of R 1   n  is 1 or 2 and each R 1  independently from any other R 1  is —CN, —CF 3 , —OCF 3 , —SCF 3 , —SOCF 3 , —SO 2 CF 3 , —F, —Cl, —Br or —I, and wherein in particular each R 1  independently from any other R 1  is —CN, —CF 3 , —SCF 3 , —SOCF 3  or —SO 2 CF 3 . 
     
     
       3. The compound according to  claim 1 , wherein n of R 1   n  is 1 or 2 and each R 1  independently from any other R 1  is —F, —Cl, —Br or —I. 
     
     
       4. The compound according to  claim 1 , wherein n of R 1   n  is 2 and each R 1  independently from any other R 1  is —CN, —CF 3 , —OCF 3 , —F, —Cl, —Br or —I and wherein in particular each R 1  independently from any other R 1  is —CN or —CF 3 . 
     
     
       5. The compound according to  claim 1 , wherein n of R 1   n  is 1 and R 1  is —CN, —CF 3 , —OCF 3 , —SCF 3 , —SOCF 3 , —SO 2 CF 3 , —F, —Cl, —Br or —I, and wherein in particular R 1  is —SCF 3 , —SOCF 3  or —SO 2 CF 3 . 
     
     
       6. The compound according to  claim 1 , wherein n is 2 and one of the two R 1  is in ortho and the other R 1  is in meta position to the attachment position of the benzene moiety, and wherein in particular one of the two R 1  is —CF 3  in ortho and the other R 1  is —CN in meta position to the attachment position of the benzene moiety. 
     
     
       7. The compound according to  claim 1 , wherein n is 1 and R 1  is in para position to the attachment position of the benzene moiety, and wherein in particular R 1  is —SCF 3 , —SOCF 3  or SO 2 CF 3  in para position to the attachment position of the benzene moiety. 
     
     
       8. The compound according to  claim 1 , wherein
 l of F l  is 0, q of K q  and p of K p  is 0 or 
 l of F l  is 0, q of K q  is 0 and K p  is C 1 -alkyl or 
 F l  is —C(═O)— with l being 1, q of K q  and p of K, are 0 or 
 F l  is —C(═O)— with l being 1, q of K q  is 0 and K p  is C 1 -alkyl. 
 
     
     
       9. The compound according to  claim 1 , wherein OM is an organometallic compound according to the general formula (2a), 
       
         
           
           
               
               
           
         
         wherein M is a metal selected from Fe, Ru, Co, Ni, Cr, Os or Mn, and 
         Y is C or N, and 
         z of R z   U  is 0, 1, 2, 3 or 4, and y of R y   L  is 0, 1, 2, 3, 4 or 5 and 
         each R L  and each R U  are independently from any other R L  and R U  selected from
 an unsubstituted or substituted C 1 -C 10  alkyl, an unsubstituted or substituted C 1 -C 10  alkenyl, an unsubstituted or substituted C 1 -C 10  alkynyl, an unsubstituted or substituted C 3 -C 8  cycloalkyl, an unsubstituted or substituted C 1 -C 10  alkoxy, an unsubstituted or substituted C 3 -C 8  cycloalkoxy, 
 an unsubstituted or substituted C 6 -C 14  aryl, 
 an unsubstituted or substituted 5- to 10-membered heteroaryl, wherein 1 to 4 ring atoms are independently selected from nitrogen, oxygen or sulfur, 
 an unsubstituted or substituted 5- to 10-membered heteroalicyclic ring, wherein 1 to 3 ring atoms are independently nitrogen, oxygen or sulfur, 
 —OR 3 , —SR 3 , —C(O)R 3 , —C(S)R 3 , —C(O)OR 3 , —C(S)OR 3 , —C(O)SR 3 , —C(O)NR 3 R 4 , —NR 3 R 4 , —S(O) 2 R 3 , —S(O) 2 OR 3  and —S(O) 2 NR 3 R 4 , 
 
         wherein 
         R 3  and R 4  are independently selected from the group consisting of hydrogen, unsubstituted C 1 -C 4  alkyl, and C 1 -C 4  alkyl substituted with C 1 -C 4  alkoxy. 
       
     
     
       10. The compound according to  claim 9 , wherein each R L  and each R U  are independently from any other R L  and R U  selected from
 —OR 3 , —SR 3 , —C(O)R 3 , —C(S)R 3 , —C(O)OR 3 , —C(S)OR 3 , —C(O)SR 3 —C(O)NR 3 R 4 , —NR 3 R 4 , —S(O) 2 R 3 , —S(O) 2 OR 3 , and —S(O) 2 NR 3 R 4 , 
 
       wherein 
       R 3  and R 4  are independently selected from the group consisting of hydrogen, unsubstituted C 1 -C 4  alkyl, and C 1 -C 4  alkyl substituted with C 1 -C 4  alkoxy. 
     
     
       11. The compound according to  claim 9 , wherein M is selected from the group of Fe, Ru or Co, wherein in particular M is Fe; and/or
 wherein Y is C; and/or 
 wherein y and z are 0. 
 
     
     
       12. The compound according  claim 1 , wherein OM is an organometallic compound according to the general formula (2b), 
       
         
           
           
               
               
           
         
         wherein M is a metal selected from the group of Mn, Re or Tc, and 
         z of R z   U  is 0, 1, 2, 3 or 4, and 
         each R U  is independently from any other R U  selected from
 an unsubstituted or substituted C 1 -C 10  alkyl, an unsubstituted or substituted C 1 -C 10  alkenyl, an unsubstituted or substituted C 1 -C 10  alkynyl, an unsubstituted or substituted C 3 -C 8  cycloalkyl, an unsubstituted or substituted C 1 -C 10  alkoxy, an unsubstituted or substituted C 3 -C 8  cycloalkoxy, 
 an unsubstituted or substituted C 6 -C 14  aryl, 
 an unsubstituted or substituted 5- to 10-membered heteroaryl, wherein 1 to 4 ring atoms per QS are independently selected from nitrogen, oxygen or sulfur, 
 an unsubstituted or substituted 5- to 10-membered heteroalicyclic ring, wherein 1 to 3 ring atoms are independently nitrogen, oxygen or sulfur, 
 —OR 3 , —SR 3 , —C(O)R 3 , —C(S)R 3 , —C(O)OR 3 , —C(S)OR 3 , —C(O)SR 3 , —C(O)NR 3 R 4 , —NR 3 R 4 , —S(O) 2 R 3 , —S(O) 2 OR 3 , and —S(O) 2 NR 3 R 4 , 
 
         wherein 
         R 3  and R 4  are independently selected from the group consisting of hydrogen, unsubstituted C 1 -C 4  alkyl, and C 1 -C 4  alkyl substituted with C 1 -C 4  alkoxy. 
       
     
     
       13. The compound according  claim 1 , wherein OM is an organometallic compound according to the general formula (2c), 
       
         
           
           
               
               
           
         
         wherein R c  is selected from
 hydrogen, 
 an unsubstituted or substituted C 1 -C 10  alkyl an unsubstituted or substituted C 1 -C 10  alkenyl, an unsubstituted or substituted C 1 -C 10  alkynyl, an unsubstituted or substituted C 3 -C 8  cycloalkyl, an unsubstituted or substituted C 1 -C 10  alkoxy, an unsubstituted or substituted C 3 -C 8  cycloalkoxy, 
 an unsubstituted or substituted C 6 -C 14  aryl, 
 an unsubstituted or substituted 5- to 10-membered heteroaryl, wherein 1 to 4 ring atoms are independently selected from nitrogen, oxygen or sulfur, 
 an unsubstituted or substituted 5- to 10-membered heteroalicyclic ring, wherein 1 to 3 ring atoms are independently nitrogen, oxygen or sulfur, 
 —OR 3 , —SR 3 , —C(O)R 3 , —C(S)R 3 , —C(O)OR 3 , —C(S)OR 3 , —C(O)SR 3 , —C(O)NR 3 R 4 , —NR 3 R 4 , —S(O) 2 R 3 , —S(O) 2 OR 3 , and —S(O) 2 NR 3 R 4 , 
 
         wherein 
         R 3  and R 4  are independently selected from the group consisting of hydrogen, unsubstituted C 1 -C 4  alkyl, and C 1 -C 4  alkyl substituted with C 1 -C 4  alkoxy. 
       
     
     
       14. A compound according to  claim 1  for use in a method of treatment of disease. 
     
     
       15. A compound according to  claim 1  for use in a method for treatment of infections by helminths,
 or for use in a method to suppress plant helminths.